The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1polymorphism with diabetic macroangiopathy

Cardiovascular Diabetology

Research

Xiaojiao Zheng¹  Rong Zhang²  Dandan Yan²  Shiyun Wang²  Zixuan Deng²  Hong Zhang²  Weiping Jia²  Cheng Hu³ 

[1]Center for Translational Medicine, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, 200233, Shanghai, People’s Republic of China

[2]Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, 600 Yishan Road, 200233, Shanghai, People’s Republic of China

[3]Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, 600 Yishan Road, 200233, Shanghai, People’s Republic of China

[4]Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, 6600 Nanfeng Road, 201499, Shanghai, People’s Republic of China

关键词: Haptoglobin;    Dimethylarginine dimethylaminohydrolase;    Asymmetric dimethylarginine;    Single nucleotide polymorphism;    Diabetic macroangiopathy;   

DOI  :  10.1186/s12933-022-01702-6

 received in 2022-08-12, accepted in 2022-11-21,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundDimethylarginine dimethylaminohydrolase (DDAH) 1 maintains the bioavailability of nitric oxide by degrading asymmetric dimethylarginine (ADMA). Here, we aimed to investigate the effect of haptoglobin (Hp) genotype on the association of ADMA and DDAH 1 polymorphism with diabetic macroangiopathy.MethodsIn stage 1, 90 Chinese participants with type 2 diabetes were enrolled to measure a panel of targeted metabolites, including ADMA, using tandem mass spectrometry (BIOCRATES AbsoluteIDQ™ p180 kit). In stage 2, an independent cohort of 2965 Chinese patients with type 2 diabetes was recruited to analyze the effect of Hp genotype on the association between DDAH 1 rs233109 and diabetic macroangiopathy. Hp genotypes were detected using a validated assay based on the TaqMan method. DDAH 1 rs233109 was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using the MassARRAY platform.ResultsIn stage 1, serum ADMA levels correlated with common Hp genotypes (β ± SE = − 0.049 ± 0.023, P = 0.035), but not with diabetic macroangiopathy (P = 0.316). In stage 2, the distribution of DDAH 1 rs233109 genotype frequencies was 15% (CC), 47% (TC), and 38% (TT), which was in Hardy-Weinberg equilibrium (P = 0.948). A significant Hp genotype by rs 233109 genotype interaction effect on diabetic macroangiopathy was found (P = 0.017). After adjusting for confounders, patients homozygous for rs233109 CC were more likely to develop diabetic macroangiopathy than those carrying TT homozygotes in the Hp 2-2 subgroup [odds ratio = 1.750 (95% confidence interval, 1.101–2.783), P = 0.018].ConclusionHp genotype affects the association between DDAH 1 rs233109 and diabetic macroangiopathy in Chinese patients with type 2 diabetes.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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